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Filipska I, Winiarska A, Knysak M, Stompór T. Contribution of Gut Microbiota-Derived Uremic Toxins to the Cardiovascular System Mineralization. Toxins (Basel) 2021; 13:toxins13040274. [PMID: 33920096 PMCID: PMC8070663 DOI: 10.3390/toxins13040274] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 04/07/2021] [Accepted: 04/08/2021] [Indexed: 02/07/2023] Open
Abstract
Chronic kidney disease (CKD) affects more than 10% of the world population and leads to excess morbidity and mortality (with cardiovascular disease as a leading cause of death). Vascular calcification (VC) is a phenomenon of disseminated deposition of mineral content within the media layer of arteries preceded by phenotypic changes in vascular smooth muscle cells (VSMC) and/or accumulation of mineral content within the atherosclerotic lesions. Medial VC results in vascular stiffness and significantly contributes to increased cardio-vascular (CV) morbidity, whereas VC of plaques may rather increase their stability. Mineral and bone disorders of CKD (CKD-MBD) contribute to VC, which is further aggravated by accumulation of uremic toxins. Both CKD-MBD and uremic toxin accumulation affect not only patients with advanced CKD (glomerular filtration rate (GFR) less than 15 mL/min/1.72 m2, end-stage kidney disease) but also those on earlier stages of a disease. The key uremic toxins that contribute to VC, i.e., p-cresyl sulphate (PCS), indoxyl sulphate (IS) and trimethylamine-N-oxide (TMAO) originate from bacterial metabolism of gut microbiota. All mentioned toxins promote VC by several mechanisms, including: Transdifferentiation and apoptosis of VSMC, dysfunction of endothelial cells, oxidative stress, interaction with local renin–angiotensin–aldosterone system or miRNA profile modification. Several attractive methods of gut microbiota manipulations have been proposed in order to modify their metabolism and to limit vascular damage (and VC) triggered by uremic toxins. Unfortunately, to date no such method was demonstrated to be effective at the level of “hard” patient-oriented or even clinically relevant surrogate endpoints.
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Winiarska A, Filipska I, Knysak M, Stompór T. Dietary Phosphorus as a Marker of Mineral Metabolism and Progression of Diabetic Kidney Disease. Nutrients 2021; 13:789. [PMID: 33673618 PMCID: PMC7997399 DOI: 10.3390/nu13030789] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 02/22/2021] [Accepted: 02/24/2021] [Indexed: 12/31/2022] Open
Abstract
Phosphorus is an essential nutrient that is critically important in the control of cell and tissue function and body homeostasis. Phosphorus excess may result in severe adverse medical consequences. The most apparent is an impact on cardiovascular (CV) disease, mainly through the ability of phosphate to change the phenotype of vascular smooth muscle cells and its contribution to pathologic vascular, valvular and other soft tissue calcification. Chronic kidney disease (CKD) is the most prevalent chronic disease manifesting with the persistent derangement of phosphate homeostasis. Diabetes and resulting diabetic kidney disease (DKD) remain the leading causes of CKD and end-stage kidney disease (ESRD) worldwide. Mineral and bone disorders of CKD (CKD-MBD), profound derangement of mineral metabolism, develop in the course of the disease and adversely impact on bone health and the CV system. In this review we aimed to discuss the data concerning CKD-MBD in patients with diabetes and to analyze the possible link between hyperphosphatemia, certain biomarkers of CKD-MBD and high dietary phosphate intake on prognosis in patients with diabetes and DKD. We also attempted to clarify if hyperphosphatemia and high phosphorus intake may impact the onset and progression of DKD. Careful analysis of the available literature brings us to the conclusion that, as for today, no clear recommendations based on the firm clinical data can be provided in terms of phosphorus intake aiming to prevent the incidence or progression of diabetic kidney disease.
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Affiliation(s)
| | | | | | - Tomasz Stompór
- Department of Nephrology, Hypertension and Internal Medicine, University of Warmia and Mazury in Olsztyn, 10561 Olsztyn, Poland; (A.W.); (I.F.); (M.K.)
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Stompór T. An Overview of the Pathophysiology of Vascular Calcification in Chronic Kidney Disease. Perit Dial Int 2020. [DOI: 10.1177/089686080702702s37] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Abnormalities of calcium–phosphate balance, with subsequent bone metabolism disorders, are among the key and earliest features of chronic kidney disease (CKD). Recently, another consequence of these abnormalities was brought to light—namely, vascular calcification. Most studies performed in patients on dialysis suggest that their vascular calcification is more advanced than that seen in the general population. Furthermore, the progression of vessel wall mineralization is much more dynamic in patients with CKD. Apart from the commonly assessed factors that promote vascular calcification, such as age, duration of dialysis, or poor control of calcium–phosphate status, several other factors have recently been identified. In the spectrum of substances involved in the regulation of the process of soft-tissue calcification, the most extensively studied in the nephrology literature are bone morphogenetic protein 7, osteoprotegerin, matrix Gla protein, fetuin-A, and the phosphatonins. Better understanding of the mechanisms underlying excess vascular mineralization have led to the development of promising new therapies.
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Affiliation(s)
- Tomasz Stompór
- Chair and Department of Nephrology, Medical Faculty, Jagiellonian University, Cracow, Poland
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4
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Abstract
End-stage renal disease patients are at a heightened risk of developing cardiovascular disease, with contributions from both “traditional” and “nontraditional” cardiovascular risk factors. Some of the nontraditional risk factors, such as extracellular volume overload, inflammation, and hyperphosphatemia, have also been shown to be important predictors of mortality in the dialysis population. This article provides an in-depth review of the evidence that supports the substantial contributions of nontraditional risk factors to adverse cardiovascular outcomes in chronic peritoneal dialysis patients. In addition, it provides evidence to demonstrate how loss of residual renal function may be central to the development of cardiovascular disease in the peritoneal dialysis population.
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Affiliation(s)
- Angela Yee-Moon Wang
- University Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong SAR, PR China
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5
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Ammirati AL, Dalboni MA, Cendoroglo M, Draibe SA, Santos RD, Miname M, Canziani MEF. The Progression and Impact of Vascular Calcification in Peritoneal Dialysis Patients. Perit Dial Int 2020. [DOI: 10.1177/089686080702700325] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
Background Progression of coronary artery calcification (CAC) has been described in hemodialysis patients, and severe CAC has been associated with the occurrence of cardiovascular events in this population. Little information is available regarding peritoneal patients. Aim To prospectively evaluate peritoneal dialysis patients in order to identify the variables associated with the rate of CAC progression, as well as to determine the impact that baseline CAC has on clinical outcomes over a 1-year follow-up period. Methods Using multislice coronary tomography, calcium scores were estimated at baseline and after 12 months in 49 peritoneal dialysis patients. Patients with and without CAC progression were compared with respect to clinical characteristics and biochemical variables, including lipid profile, parameters of mineral metabolism, and markers of inflammation. Cardiovascular events, hospitalizations, and all-cause mortality were recorded. Results At baseline, 29 patients (59%) presented CAC and a median calcium score of 234.7 (range 10.3 – 2351) Agatston units. Progression of CAC was observed in 13 patients (43%) who, in comparison with those presenting no CAC progression, were older, presented higher baseline calcium scores, and had higher mean glucose levels, lower mean high density lipoprotein cholesterol levels, and more months using low calcium peritoneal solution. We also observed a trend toward more often presenting with a history of hypertension, exhibiting more hyperphosphatemic and hyperglycemic events, and having lower albumin levels. In multiple logistic regression, only baseline calcium score was independently associated with progression of CAC. A shorter cardiovascular event-free time and a trend toward lower survival rates were observed in the group with CAC. Hospitalization event-free time did not differ between the groups. Conclusion Determining CAC provides important prognostic data in peritoneal dialysis patients. Baseline calcium score and disturbances in glucose, mineral, and lipid metabolism were indicative of higher risk of CAC progression in this population.
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Affiliation(s)
| | | | | | | | - Raul D. Santos
- The Lipid Clinic of the Heart Institute (InCor), University of São Paulo, São Paulo, Brazil
| | - Márcio Miname
- The Lipid Clinic of the Heart Institute (InCor), University of São Paulo, São Paulo, Brazil
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6
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Wei M, Esbaei K, Bargman J, Oreopoulos DG. Relationship between Serum Magnesium, Parathyroid Hormone, and Vascular Calcification in Patients on Dialysis: A Literature Review. Perit Dial Int 2020. [DOI: 10.1177/089686080602600315] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Secondary hyperparathyroidism is present in most patients with end-stage renal disease and has been linked to uremic bone disease, vascular calcification, and mortality. Current literature suggests an association between hypomagnesemia and cardiovascular disease in the general population. We reviewed all published studies on the relationship between serum magnesium and parathyroid hormone and the relationship between serum Mg and vascular calcification in dialysis patients. Of these, 10 of 12 studies of patients on hemodialysis and 4 of 5 studies of patients on peritoneal dialysis showed a significant inverse relationship between serum Mg and serum intact parathyroid hormone. Hyperparathyroidism develops in peritoneal dialysis patients dialyzed with a solution containing normal calcium (1.25 mmol/L) and low Mg (0.25 mmol/L), even though serum calcium is maintained at a normal level. Four of the hemodialysis studies and one of the peritoneal dialysis studies indicated that there is an inverse relationship between serum Mg and vascular calcification in these patients. Potential benefits have been attributed to magnesium carbonate as a phosphate binder and it may possibly be an effective, less toxic, less expensive phosphate binder. We believe that the role of Mg in secondary hyperparathyroidism and vascular calcification merits further investigation.
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Affiliation(s)
- Mingxin Wei
- Home Peritoneal Dialysis Unit, University Health Network and University of Toronto, Toronto, Ontario, Canada
- Department of Nephrology, Guangxi People's Hospital, Guangxi, P. R. China
| | - Khaled Esbaei
- Home Peritoneal Dialysis Unit, University Health Network and University of Toronto, Toronto, Ontario, Canada
- Al-Fatah University, Tripoli Central Hospital, Tripoli, Libya
| | - Joanne Bargman
- Home Peritoneal Dialysis Unit, University Health Network and University of Toronto, Toronto, Ontario, Canada
| | - Dimitrios G. Oreopoulos
- Home Peritoneal Dialysis Unit, University Health Network and University of Toronto, Toronto, Ontario, Canada
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Abstract
The CANUSA study originally reported the importance of total small-solute clearance in predicting survival of peritoneal dialysis (PD) patients. However, subsequent reanalysis of data from the CANUSA study clearly demonstrated that the predictive power for mortality in PD patients was largely attributable to residual renal function (RRF) and not to the dose of PD. While this should not lead to the assumption that the dose of PD is unimportant, it does clearly indicate that the contribution of residual renal clearance and PD clearance to the overall survival of PD cannot be considered equivalent. In a previous study, we also demonstrated the importance of loss of RRF in predicting a heightened risk of mortality and cardiovascular death in PD patients. In this review, we focus our discussion on the different potential mechanisms that explain the important link between RRF and cardiovascular disease and survival of PD patients. We provide evidence to explain why RRF is so important to patients receiving long-term PD treatment and why it should be regarded as the “heart” of PD.
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Affiliation(s)
- Angela Yee-Moon Wang
- University Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong, China
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Xu D, Zeng F, Han L, Wang J, Yin Z, Lv L, Guo L, Wang D, Xu Y, Zhou H. The synergistic action of phosphate and interleukin-6 enhances senescence-associated calcification in vascular smooth muscle cells depending on p53. Mech Ageing Dev 2019; 182:111124. [PMID: 31376399 DOI: 10.1016/j.mad.2019.111124] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2019] [Revised: 06/07/2019] [Accepted: 07/22/2019] [Indexed: 02/07/2023]
Abstract
Cardiovascular calcification is associated with cardiovascular morbidity and mortality of patients with end-stage renal diseases (ESRD). Hyperphosphatemia and many of the inflammatory markers and mediators, including interleukin-6 (IL-6), are considered as the major risk factors of cardiovascular calcification. Although cellular senescence may be involved in cardiovascular calcification caused by phosphate overload and (or) IL-6 in patients with ESRD, less is known about the underlying mechanisms for phosphate- and IL-6-induced senescence-associated calcification of vascular smooth muscle cells (VSMCs). In the present study, we investigated the correlation between cellular senescence and vascular calcification induced by loading phosphate and (or) IL-6 in VSMCs. Our findings show that p53 plays a major role in senescence-associated vascular calcification induced by phosphate overload. IL-6 induces senescence-associated calcification in VSMCs depending upon activation of the IL-6/soluble IL-6 receptor (sIL-6R)/signal transducer and activator of transcription 3 (STAT3)/p53/p21 pathway. We demonstrate that the synergistic action of phosphate overload and IL-6 enhances senescence-associated calcification in a p53-dependent manner and is inhibited by an anti-aging agent (resveratrol) in a dose-dependent manner.
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Affiliation(s)
- Deping Xu
- Clinical Laboratory, The First Affiliated Hospital, Anhui Medical University (AHMU). No. 81 Meishan Rd., Hefei, China; Department of Biochemistry & Molecular Biology, AHMU. No. 69 Meishan Rd., Hefei, China
| | - Fanjun Zeng
- Department of Biochemistry & Molecular Biology, AHMU. No. 69 Meishan Rd., Hefei, China
| | - Linzi Han
- Department of Biochemistry & Molecular Biology, AHMU. No. 69 Meishan Rd., Hefei, China; Department of Nephrology, The Second Affiliated Hospital, AHMU. No. 678 Furong Rd., Hefei, China
| | - Jun Wang
- Department of Nephrology, The Second Affiliated Hospital, AHMU. No. 678 Furong Rd., Hefei, China
| | - Zongzhi Yin
- Department of Obstetrics and Gynaecology, The First Affiliated Hospital, AHMU. No. 81 Meishan Rd., Hefei, China
| | - Liying Lv
- Clinical Laboratory, The First Affiliated Hospital, Anhui Medical University (AHMU). No. 81 Meishan Rd., Hefei, China
| | - Liyu Guo
- Department of Biochemistry & Molecular Biology, AHMU. No. 69 Meishan Rd., Hefei, China
| | - Deguang Wang
- Department of Nephrology, The Second Affiliated Hospital, AHMU. No. 678 Furong Rd., Hefei, China.
| | - Yuanhong Xu
- Clinical Laboratory, The First Affiliated Hospital, Anhui Medical University (AHMU). No. 81 Meishan Rd., Hefei, China.
| | - Haisheng Zhou
- Department of Biochemistry & Molecular Biology, AHMU. No. 69 Meishan Rd., Hefei, China; Center for Scientific Research, AHMU. No. 81 Meishan Rd., Hefei, China.
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9
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Jansz TT, Verhaar MC, London GM, van Jaarsveld BC. Is progression of coronary artery calcification influenced by modality of renal replacement therapy? A systematic review. Clin Kidney J 2018; 11:353-361. [PMID: 29942499 PMCID: PMC6007793 DOI: 10.1093/ckj/sfx124] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2017] [Accepted: 09/12/2017] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Progression of coronary artery calcification is an important marker for cardiovascular morbidity in end-stage renal disease patients. Therefore, we reviewed the evidence on coronary artery calcification progression in different renal replacement therapies. METHODS MEDLINE (PubMed), Embase and TRIP databases were searched from 1999 - 2016. Additionally, bibliographies were searched by hand and citation tracking of key publications was performed. Prospective studies were included that examined coronary artery calcification with two or more multislice computed tomography scans ≥6 months apart in patients 18-75 years old receiving any renal replacement therapy, including kidney transplantation. Reporting of separate scores for different modalities was required. Two researchers extracted data independently with pilot-tested forms and assessed the risk of bias using a validated tool. RESULTS We identified 29 eligible studies that assessed coronary artery calcification progression in end-stage renal disease patients, of which 19 studies evaluated haemodialysis and 8 kidney transplantation. Evidence on progression in peritoneal dialysis (three studies) and nocturnal haemodialysis (one study) was limited. Meta-analysis was not possible due to diverse reporting methods of coronary artery calcification scores and definitions of progression. Median coronary artery calcification scores were considerably higher in haemodialysis cohorts at baseline, presumably due to a generally higher age and dialysis vintage. Median coronary artery calcification progressed universally. Visual inspection suggested the least progression in kidney transplant recipients. CONCLUSIONS There is insufficient evidence to compare the influence of renal replacement therapies on coronary artery calcification progression. We advocate the adoption of a standardized reporting method of coronary artery calcification progression.
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Affiliation(s)
- Thijs T Jansz
- Department of Nephrology and Hypertension, University Medical Centre Utrecht, Utrecht, The Netherlands
| | - Marianne C Verhaar
- Department of Nephrology and Hypertension, University Medical Centre Utrecht, Utrecht, The Netherlands
| | - Gérard M London
- INSERM U970, Hôpital Européen Georges Pompidou, Paris, France
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10
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Smerud KT, Åsberg A, Kile H, Pasch A, Dahle DO, Bollerslev J, Godang K, Hartmann A. A rapid and sustained improvement of calcification propensity score (serum T 50 ) after successful kidney transplantation: Reanalysis of a randomized controlled trial of ibandronate. Clin Transplant 2017; 31. [PMID: 28972673 DOI: 10.1111/ctr.13131] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/13/2017] [Indexed: 12/12/2022]
Abstract
A serum test called T50 assesses the overall propensity for calcification of the blood and is associated with cardiovascular outcomes. We aimed to examine T50 over time in kidney transplant recipients and also address any effects of ibandronate. Serum samples taken from kidney transplant patients included in a prospective, randomized placebo controlled study of ibandronate were analyzed in retrospect. Adequate analyses were performed at baseline (approximately 3 weeks after transplantation) in 129 patients, at 10 weeks in 127 patients and at 1 year in 123 patients. There were no statistical differences between ibandronate and placebo treatment in terms of T50 at 10 weeks (P = .094) or at 1 year (P = .116). Baseline T50 was a significant covariate (P < .0001) for T50 scores at 10 weeks and 1 year. In the total cohort, there was a highly significant (P < .0001) increase in T50 of 26.6% after 10 weeks and T50 remained stable after 1 year. T50 change was inversely correlated to phosphate of -0.515 (P < .0001) and to change in serum albumin (P < .03). We found that T50 increased from baseline to 10 weeks after transplantation with no further change after 1 year. Ibandronate had no effect on T50 .
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Affiliation(s)
- Knut T Smerud
- Department of Transplantation Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.,Smerud Medical Research International AS, Oslo, Norway
| | - Anders Åsberg
- Department of Transplantation Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.,The Norwegian Renal Registry, Oslo University Hospital, Rikshospitalet, Oslo, Norway.,School of Pharmacy, University of Oslo, Oslo, Norway
| | - Håkon Kile
- Smerud Medical Research International AS, Oslo, Norway
| | | | - Dag O Dahle
- Department of Transplantation Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway
| | - Jens Bollerslev
- Section of Specialized Endocrinology, Department of Endocrinology, Oslo University Hospital, Oslo, Norway.,Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
| | - Kristin Godang
- Section of Specialized Endocrinology, Department of Endocrinology, Oslo University Hospital, Oslo, Norway
| | - Anders Hartmann
- Department of Transplantation Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.,Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
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11
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Ye H, Zhou Q, Fan L, Guo Q, Mao H, Huang F, Yu X, Yang X. The impact of peritoneal dialysis-related peritonitis on mortality in peritoneal dialysis patients. BMC Nephrol 2017; 18:186. [PMID: 28583107 PMCID: PMC5460447 DOI: 10.1186/s12882-017-0588-4] [Citation(s) in RCA: 72] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2017] [Accepted: 05/16/2017] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Results concerning the association between peritoneal dialysis-related peritonitis and mortality in peritoneal dialysis patients are inconclusive, with one potential reason being that the time-dependent effect of peritonitis has rarely been considered in previous studies. This study aimed to evaluate whether peritonitis has a negative impact on mortality in a large cohort of peritoneal dialysis patients. We also assessed the changing impact of peritonitis on patient mortality with respect to duration of follow-up. METHODS This retrospective cohort study included incident patients who started peritoneal dialysis from 1 January 2006 to 31 December 2011. Episodes of peritonitis were recorded at the time of onset, and peritonitis was parameterized as a time-dependent variable for analysis. We used the Cox regression model to assess whether peritonitis has a negative impact on mortality. RESULTS A total of 1321 patients were included. The mean age was 48.1 ± 15.3 years, 41.3% were female, and 23.5% with diabetes mellitus. The median (interquartile) follow-up time was 34 (21-48) months. After adjusting for confounders, peritonitis was independently associated with 95% increased risk of all-cause mortality (hazard ratio, 1.95; 95% confidence interval: 1.46-2.60), 90% increased risk of cardiovascular mortality (hazard ratio, 1.90; 95% confidence interval: 1.28-2.81) and near 4-fold increased risk of infection-related mortality (hazard ratio, 4.94; 95% confidence interval: 2.47-9.86). Further analyses showed that peritonitis was not significantly associated with mortality within 2 years of peritoneal dialysis initiation, but strongly influenced mortality in patients dialysed longer than 2 years. CONCLUSIONS Peritonitis was independently associated with higher risk of all-cause, cardiovascular and infection-related mortality in peritoneal dialysis patients, and its impact on mortality was more significant in patients with longer peritoneal dialysis duration.
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Affiliation(s)
- Hongjian Ye
- Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, 58th, Zhongshan Road II, Guangzhou, 510080, China.,Key Laboratory of Nephrology, Ministry of Health, Guangzhou, 510080, China.,Guangdong Provincial Key Laboratory of Nephrology, Guangzhou, 510080, China
| | - Qian Zhou
- Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, 58th, Zhongshan Road II, Guangzhou, 510080, China.,Key Laboratory of Nephrology, Ministry of Health, Guangzhou, 510080, China.,Guangdong Provincial Key Laboratory of Nephrology, Guangzhou, 510080, China.,Epidemiology Research Unit, The First Affiliated Hospital, Sun Yat-sen University, 58th, Zhongshan Road II, Guangzhou, 510080, China
| | - Li Fan
- Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, 58th, Zhongshan Road II, Guangzhou, 510080, China.,Key Laboratory of Nephrology, Ministry of Health, Guangzhou, 510080, China.,Guangdong Provincial Key Laboratory of Nephrology, Guangzhou, 510080, China
| | - Qunying Guo
- Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, 58th, Zhongshan Road II, Guangzhou, 510080, China.,Key Laboratory of Nephrology, Ministry of Health, Guangzhou, 510080, China.,Guangdong Provincial Key Laboratory of Nephrology, Guangzhou, 510080, China
| | - Haiping Mao
- Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, 58th, Zhongshan Road II, Guangzhou, 510080, China.,Key Laboratory of Nephrology, Ministry of Health, Guangzhou, 510080, China.,Guangdong Provincial Key Laboratory of Nephrology, Guangzhou, 510080, China
| | - Fengxian Huang
- Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, 58th, Zhongshan Road II, Guangzhou, 510080, China.,Key Laboratory of Nephrology, Ministry of Health, Guangzhou, 510080, China.,Guangdong Provincial Key Laboratory of Nephrology, Guangzhou, 510080, China
| | - Xueqing Yu
- Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, 58th, Zhongshan Road II, Guangzhou, 510080, China.,Key Laboratory of Nephrology, Ministry of Health, Guangzhou, 510080, China.,Guangdong Provincial Key Laboratory of Nephrology, Guangzhou, 510080, China
| | - Xiao Yang
- Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, 58th, Zhongshan Road II, Guangzhou, 510080, China. .,Key Laboratory of Nephrology, Ministry of Health, Guangzhou, 510080, China. .,Guangdong Provincial Key Laboratory of Nephrology, Guangzhou, 510080, China.
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12
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Chen Z, Qureshi AR, Parini P, Hurt-Camejo E, Ripsweden J, Brismar TB, Barany P, Jaminon AM, Schurgers LJ, Heimbürger O, Lindholm B, Stenvinkel P. Does statins promote vascular calcification in chronic kidney disease? Eur J Clin Invest 2017; 47:137-148. [PMID: 28036114 DOI: 10.1111/eci.12718] [Citation(s) in RCA: 50] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2016] [Accepted: 12/28/2016] [Indexed: 12/19/2022]
Abstract
BACKGROUND In end-stage renal disease (ESRD), coronary artery calcification (CAC) and inflammation contribute to cardiovascular disease (CVD). Statins do not improve survival in patients with ESRD, and their effect on vascular calcification is unclear. We explored associations between CAC, inflammatory biomarkers, statins and mortality in ESRD. MATERIALS AND METHODS In 240 patients with ESRD (63% males; median age 56 years) from cohorts including 86 recipients of living donor kidney transplant (LD-Rtx), 96 incident dialysis patients and 58 prevalent peritoneal dialysis patients, associations of CAC score (Agatston Units, AUs), interleukin-6 (IL-6) with high-sensitivity C-reactive protein (hsCRP), tumour necrosis factor (TNF), use of statins and all-cause mortality were analysed. Cardiac CT was repeated in 35 patients after 1·5 years of renal replacement therapy. In vitro, human vascular smooth muscle cells (hVSMCs) were used to measure vitamin K metabolism. RESULTS Among 240 patients, 129 (53%) had a CAC score > 100 AUs. Multivariate analysis revealed that independent predictors of 1-SD higher CAC score were age, male gender, diabetes and use of statins. The association between CAC score and mortality remained significant after adjustment for age, gender, diabetes, CVD, use of statins, protein-energy wasting and inflammation. Repeated CAC imaging in 35 patients showed that statin therapy was associated with greater progression of CAC. In vitro synthesis of menaquinone-4 by hVSMCs was significantly impaired by statins. CONCLUSION Elevated CAC score is a mortality risk factor in ESRD independent of inflammation. Future studies should resolve if statins promote vascular calcification and inhibition of vitamin K synthesis in the uremic milieu.
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Affiliation(s)
- Zhimin Chen
- Kidney Disease Center, First Affiliated Hospital College of Medicine, Zhejiang University, Hangzhou, China.,Division of Renal Medicine and Baxter Novum, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
| | - Abdul Rashid Qureshi
- Division of Renal Medicine and Baxter Novum, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
| | - Paolo Parini
- Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.,Metabolism Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Eva Hurt-Camejo
- Translational Science, CVMD iMed, AstraZeneca R&D, Gothenburg, Sweden
| | - Jonaz Ripsweden
- Division of Medical Imaging and Technology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden.,Department of Radiology, Karolinska University Hospital, Huddinge, Stockholm, Sweden
| | - Torkel B Brismar
- Division of Medical Imaging and Technology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden.,Department of Radiology, Karolinska University Hospital, Huddinge, Stockholm, Sweden
| | - Peter Barany
- Division of Renal Medicine and Baxter Novum, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
| | - Armand M Jaminon
- Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands
| | - Leon J Schurgers
- Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands
| | - Olof Heimbürger
- Division of Renal Medicine and Baxter Novum, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
| | - Bengt Lindholm
- Division of Renal Medicine and Baxter Novum, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
| | - Peter Stenvinkel
- Division of Renal Medicine and Baxter Novum, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
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Sharaf El Din UAA, Salem MM, Abdulazim DO. Vascular calcification: When should we interfere in chronic kidney disease patients and how? World J Nephrol 2016; 5:398-417. [PMID: 27648404 PMCID: PMC5011247 DOI: 10.5527/wjn.v5.i5.398] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2016] [Revised: 04/20/2016] [Accepted: 06/27/2016] [Indexed: 02/06/2023] Open
Abstract
Chronic kidney disease (CKD) patients are endangered with the highest mortality rate compared to other chronic diseases. Cardiovascular events account for up to 60% of the fatalities. Cardiovascular calcifications affect most of the CKD patients. Most of this calcification is related to disturbed renal phosphate handling. Fibroblast growth factor 23 and klotho deficiency were incriminated in the pathogenesis of vascular calcification through different mechanisms including their effects on endothelium and arterial wall smooth muscle cells. In addition, deficient klotho gene expression, a constant feature of CKD, promotes vascular pathology and shares in progression of the CKD. The role of gut in the etio-pathogenesis of systemic inflammation and vascular calcification is a newly discovered mechanism. This review will cover the medical history, prevalence, pathogenesis, clinical relevance, different tools used to diagnose, the ideal timing to prevent or to withhold the progression of vascular calcification and the different medications and medical procedures that can help to prolong the survival of CKD patients.
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14
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Shang D, Xie Q, Ge X, Yan H, Tian J, Kuang D, Hao CM, Zhu T. Hyperphosphatemia as an independent risk factor for coronary artery calcification progression in peritoneal dialysis patients. BMC Nephrol 2015; 16:107. [PMID: 26187601 PMCID: PMC4506628 DOI: 10.1186/s12882-015-0103-8] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2014] [Accepted: 06/30/2015] [Indexed: 12/15/2022] Open
Abstract
Background Coronary artery calcification (CAC) is associated with cardiovascular mortality in end-stage renal disease (ESRD) patients. The present study aimed to identify modifiable risk factors for CAC progression in peritoneal dialysis (PD) patients. Methods Adult patients who received regular PD for more than 6 months and underwent a series of coronary artery calcification score (CaCS) measurements by multislice spiral computed tomography (MSCT) with an interval of ≥ 6 months were included in this observational cohort study. The demographic characteristics and clinical data, including laboratory data and adequacy of PD, were collected. Curve estimation was used to fit the straight line and obtain the slope. Binary logistic regression was performed to identify the independent risk factors for CAC progression in the PD patients, and multivariate linear regression was conducted to identify factors associated with hyperphosphatemia. Results A total of 207 adult patients on PD (116 men, 56.0 %) with a mean age of 59.8 ± 15.9 years were recruited to this study, and 157 of them (75.8 %) received three or more CaCS assessments. The patients were divided into a slow group (n = 137) and a rapid group (n = 70) according to the linear regression slope or the average speed of development. The follow-up time was 33.0 ± 18.8 months. Multivariate logistic regression revealed that age and serum phosphate level were independent risk factors for CAC progression after adjustments. Multivariate linear regression revealed that hyperphosphatemia was associated with elevations in the transferrin and serum albumin levels and normalized protein catabolic rate (nPCR) and reductions in the hemoglobin level, residual Ccr, and PD Ccr. Conclusions Hyperphosphatemia is an independent risk factor for CAC progression, and the serum phosphate level may be associated with protein intake and PD adequacy. These results provide important information for the clinical management of ESRD patients.
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Affiliation(s)
- Da Shang
- Division of Nephrology, Huashan Hospital, Fudan University, 12 Wulumuqi Road (middle), Shanghai, 200040, China.
| | - Qionghong Xie
- Division of Nephrology, Huashan Hospital, Fudan University, 12 Wulumuqi Road (middle), Shanghai, 200040, China.
| | - Xiaolin Ge
- Division of Nephrology, Huashan Hospital, Fudan University, 12 Wulumuqi Road (middle), Shanghai, 200040, China.
| | - Huanqing Yan
- Division of Nephrology, Huashan Hospital Baoshan Branch, Fudan University, Shanghai, 200443, China.
| | - Jing Tian
- Division of Nephrology, Huashan Hospital, Fudan University, 12 Wulumuqi Road (middle), Shanghai, 200040, China.
| | - Dingwei Kuang
- Division of Nephrology, Huashan Hospital, Fudan University, 12 Wulumuqi Road (middle), Shanghai, 200040, China.
| | - Chuan-Ming Hao
- Division of Nephrology, Huashan Hospital, Fudan University, 12 Wulumuqi Road (middle), Shanghai, 200040, China.
| | - Tongying Zhu
- Division of Nephrology, Huashan Hospital, Fudan University, 12 Wulumuqi Road (middle), Shanghai, 200040, China. .,Division of Nephrology, Huashan Hospital Baoshan Branch, Fudan University, Shanghai, 200443, China.
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15
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Ishimura E, Okuno S, Okazaki H, Norimine K, Yamakawa K, Yamakawa T, Shoji S, Nishizawa Y, Inaba M. Significant Association Between Bone-Specific Alkaline Phosphatase and Vascular Calcification of the Hand Arteries in Male Hemodialysis Patients. Kidney Blood Press Res 2014; 39:299-307. [DOI: 10.1159/000355807] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/18/2014] [Indexed: 11/19/2022] Open
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Karohl C, D'Marco Gascón L, Raggi P. Noninvasive imaging for assessment of calcification in chronic kidney disease. Nat Rev Nephrol 2011; 7:567-77. [PMID: 21862991 DOI: 10.1038/nrneph.2011.110] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Vascular calcification is highly prevalent in patients with chronic kidney disease and has a progressive course. Several cardiovascular and uremia-related risk factors, such as abnormalities in mineral metabolism, contribute to the development of vascular calcification, although the pathophysiological mechanisms are still unclear. The presence and extent of vascular calcification is associated with an increased risk of cardiovascular events and mortality. By contrast, patients who do not have calcification seem to have a good prognosis, with minimal or no calcification progression over an extended period of time. A number of noninvasive imaging methods are available to detect vascular calcification and may help clinicians to make therapeutic decisions. Cardiac CT remains the reference standard to detect and quantify coronary artery, aortic and cardiac valve calcification. However, the high cost of equipment, the inability to perform in-office testing and the expertise required limit its use on a routine basis. Other imaging methods, such as planar X-ray, ultrasound and echocardiography, are appropriate alternatives to evaluate vascular and valvular calcification. In this review, we discuss the noninvasive imaging methods most frequently used to assess vascular and valvular calcification, with their advantages and limitations.
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Affiliation(s)
- Cristina Karohl
- Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Avenida Paulo Gama 110, Porto Alegre, RS 90040-060, Brazil
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17
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Bhan I, Thadhani R. Vascular calcification and ESRD: a hard target. Clin J Am Soc Nephrol 2010; 4 Suppl 1:S102-5. [PMID: 19995990 DOI: 10.2215/cjn.04800709] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
End-stage renal disease (ESRD) is associated with both accelerated cardiovascular disease and alterations in vitamin D and mineral metabolism. Calcification of both coronary and extra-cardiac vessels is common in ESRD. Several studies suggest that vascular calcification is associated with coronary atherosclerosis, vascular wall stiffness, left ventricular hypertrophy, and subsequent increased mortality, but it is not yet clear if vascular calcification is a direct cause of these changes or merely a marker of disease. Reviewed here is the current state of research on the biology and the significance of vascular calcification in ESRD, the role of vitamin D therapy in its development, and options for management.
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Affiliation(s)
- Ishir Bhan
- Department of Medicine, Massachusetts General Hospital, Bullfinch 127, Boston, MA 02114, USA
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18
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O'Neill WC, Sigrist MK, McIntyre CW. Plasma pyrophosphate and vascular calcification in chronic kidney disease. Nephrol Dial Transplant 2009; 25:187-91. [PMID: 19633093 DOI: 10.1093/ndt/gfp362] [Citation(s) in RCA: 114] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND Pyrophosphate (PPi) is a potent inhibitor of vascular calcification and may be deficient in renal failure. We sought to determine whether plasma PPi is affected by dialysis or the mode of dialysis and whether it correlates with vascular calcification. METHODS PPi was measured in plasma samples stored from a recent study of vascular calcification in 54 HD patients, 23 peritoneal dialysis (PD) patients and 38 patients with stage 4 chronic kidney disease (CKD). Calcification was quantified in a standardized section of the superficial femoral artery using computed tomography, and PPi was measured by enzyme assay, at both baseline and 1 year. RESULTS Baseline plasma PPi was weakly correlated with age and serum phosphate, but not with alkaline phosphatase activity or other biochemical parameters, and did not differ between HD, PD and CKD patients. Both baseline calcification score and change in the calcification score at 1 year decreased with increasing quartiles of plasma PPi. In a multivariate analysis, plasma PPi was independently correlated with baseline calcification (P = 0.039) and the change in calcification (P = 0.029). CONCLUSION Plasma PPi is negatively associated with vascular calcification in end-stage renal disease (ESRD) and CKD but is not affected by dialysis, the mode of dialysis or nutritional or inflammatory status. Although these data are consistent with an inhibitory effect of PPi on vascular calcification, further studies are needed to establish a causal role.
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Affiliation(s)
- W Charles O'Neill
- Renal Division, Department of Medicine, Emory University, Atlanta, GA, USA.
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19
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Abstract
Cardiovascular disease is the leading cause of mortality in patients with end-stage renal disease (ESRD) and is attributed to a combination of traditional and non-traditional cardiovascular risk factors. In recent years, there has also been an increasing recognition of a very high prevalence of cardiovascular calcification in the ESRD population, including in patients receiving long-term peritoneal dialysis (PD). Numerous observational cohort studies have demonstrated the prognostic importance of cardiovascular calcifications in these patients. The mechanisms are not completely understood, but are likely multifactorial. The present article reviews the prevalence, clinical course, prognostic significance, and some contributing factors for vascular and valvular calcification in ESRD patients, including patients receiving PD therapy.
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Affiliation(s)
- Angela Yee-Moon Wang
- University Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong SAR, PR China
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20
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Evenepoel P, Selgas R, Caputo F, Foggensteiner L, Heaf JG, Ortiz A, Kelly A, Chasan-Taber S, Duggal A, Fan S. Efficacy and safety of sevelamer hydrochloride and calcium acetate in patients on peritoneal dialysis. Nephrol Dial Transplant 2008; 24:278-85. [DOI: 10.1093/ndt/gfn488] [Citation(s) in RCA: 60] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
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Ammirati AL, Moysés RMA, Canziani ME. Vascular Calcification in Peritoneal Dialysis Patients. Perit Dial Int 2008. [DOI: 10.1177/089686080802802s04] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
Vascular calcification (VC) is being recognized as a common complication at all stages of chronic kidney disease, particularly in patients on dialysis. Traditional and nontraditional cardiovascular risk factors both appear to be involved in the development of VC in this population. Although few studies focusing exclusively on peritoneal dialysis (PD) patients are available, some data support the view that VC constitutes an independent prognostic marker of morbidity and mortality in the PD population. In this review, we discuss the potential pathophysiologic pathways of VC in PD patients, and we examine the relevant clinical data.
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Sigrist MK, Taal MW, Bungay P, McIntyre CW. Progressive vascular calcification over 2 years is associated with arterial stiffening and increased mortality in patients with stages 4 and 5 chronic kidney disease. Clin J Am Soc Nephrol 2007; 2:1241-8. [PMID: 17928470 DOI: 10.2215/cjn.02190507] [Citation(s) in RCA: 231] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND AND OBJECTIVES Vascular calcification is increasingly recognized as an important component of cardiovascular disease in chronic kidney disease. The objective of this study was to investigate prospectively the determinants, cardiovascular functional consequences, and survival associated with vascular calcification over 24 mo. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A total of 134 patients (60 on hemodialysis, 28 on peritoneal dialysis, and 46 with stage 4 chronic kidney disease) were studied. Vascular calcification of the superficial femoral artery was assessed using multislice spiral computed tomography; pulse wave velocity; all medications and time-averaged biochemical parameters were recorded at baseline and 12 and 24 mo. RESULTS A total of 101 patients remained at 24 mo. Progressive calcification was seen in 58 of 101 patients. Most (31 of 46) patients with an initial calcification score of zero did not develop calcification. The hemodialysis group demonstrated a greater degree of progression than patients who were on peritoneal dialysis or had stage 4 chronic kidney disease. Progressive calcification was associated with age, male gender, serum alkaline phosphatase, beta blockers, and lipid-lowering agents. Increases in vascular calcification correlated with increased arterial stiffness. Vascular calcification was present in 20 of 21 patients who died. Cox proportional hazard analysis identified change in calcification score, calcium intake from phosphate binders, and low albumin as risk factors for death. CONCLUSIONS Patients with stages 4 and 5 chronic kidney disease and preexisting vascular calcification exhibit significantly increased calcification over 24 mo. Rapid progression of calcification is associated with arterial stiffness and mortality.
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Affiliation(s)
- Mhairi K Sigrist
- Department of Renal Medicine, Derby City General Hospital, Derby, DE22 3NE, UK
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23
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Abstract
Scattered through the practice of medicine are dogmas with little or no scientific basis. One of these is the product of the serum calcium and phosphorus concentrations, the so-called calcium-phosphorus product or Ca x P. The assumption that ectopic calcification will occur when the product of the serum calcium and phosphorus concentrations exceeds a particular threshold has become standard practice in nephrology even though there is little scientific basis. Experimental support is lacking, the chemistry underlying the use of the product is oversimplified and the concept that ectopic calcification is simply the result of supersaturation is biologically flawed. The evidence that the Ca x P is an independent risk factor for mortality and morbidity is also questionable. Although ectopic calcification can occur in many sites, this review will focus on vascular calcification, as it is the most common site and the site most likely to affect patient outcomes.
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Affiliation(s)
- W C O'Neill
- Department of Medicine, Renal Division, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
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24
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Wei M, Taskapan H, Esbaei K, Jassal SV, Bargman JM, Oreopoulos DG. K/DOQI guideline requirements for calcium, phosphate, calcium phosphate product, and parathyroid hormone control in dialysis patients: can we achieve them? Int Urol Nephrol 2006; 38:739-43. [PMID: 17160632 DOI: 10.1007/s11255-005-0083-x] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/14/2005] [Indexed: 11/29/2022]
Abstract
BACKGROUND Mineral metabolism has emerged as an important predictor of morbidity and mortality in dialysis patients. Kidney Disease Outcomes Quality Initiative (K/DOQI) clinical practice guidelines for bone metabolism and disease in chronic kidney disease (CKD) recommend that, in Stage 5 CKD, the target levels for calcium (Ca) (corrected for serum albumin), phosphate (P), calcium x phosphate (CaxP) product and parathyroid hormone (PTH) levels should be maintained at 8.4-9.5 mg/dl, 3.5-5.5 mg/dl, <55 mg2/dl2 and 150-300 pg/ml, respectively. OBJECTIVES To evaluate our ability to achieve K/DOQI guidelines for bone metabolism and disease targets in our patients and to compare them between patients on hemodialysis (HD) and peritoneal dialysis (PD) and also with those reported in the literature. METHODS We reviewed bone metabolism laboratory parameters in 57 HD patients and 69 PD patients, who had been on dialysis for more than 9 months. RESULTS The percentage of patients whose serum Ca, P, CaxP product and PTH were within K/DOQI recommended target ranges were 46%, 53%, 77% and 28% in HD patients and 52%, 65%, 77% and 23% in PD patients, respectively. There were no significant differences between HD and PD patients in the percentage of all parameters that were within K/DOQI recommended target ranges. The percentage of our HD patients who had Ca, P, and PTH levels within recommended target range was similar to those in previous reports. CONCLUSION In our unit, the management of bone and mineral metabolism in HD and PD patients is still far short of meeting K/DOQI guidelines. These findings appear similar in HD and PD patients. Our findings resemble those reported in the literature.
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Affiliation(s)
- Mingxin Wei
- Home Peritoneal Dialysis Unit, University Health Network and University of Toronto, Toronto, Ontario, Canada, and Department of Nephrology, Guangxi People's Hospital, Guangxi, PR China.
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25
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Garland JS, Morton AR. Sevelamer Hydrochloride in Peritoneal Dialysis Patients: CA’ Canny but CA’ AWA’. Perit Dial Int 2006. [DOI: 10.1177/089686080602600303] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Affiliation(s)
- Jocelyn S. Garland
- Division of Nephrology Department of Medicine Queen's University Kingston, Ontario, Canada
| | - A. Ross Morton
- Division of Nephrology Department of Medicine Queen's University Kingston, Ontario, Canada
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Dellegrottaglie S, Sanz J, Rajagopalan S. Vascular calcification in patients with chronic kidney disease. Blood Purif 2006; 24:56-62. [PMID: 16361842 DOI: 10.1159/000089438] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Chronic kidney disease (CKD) represents an extremely common condition, and cardiovascular diseases are frequently reported in this patient population. Traditional risk factors are not accurate prognostic predictors in CKD patients, and new potential markers to predict the cardiovascular involvement in uremic patients need to be identified. Vascular calcification (VC) represents a hallmark of the atherosclerotic process in CKD. This review summarizes the processes responsible for VC (particularly focusing on the mechanisms operative in the presence of renal dysfunction), discusses the utility of computer tomography modalities in the detection of VC in patients with CKD, and reports the potential role of VC as pathophysiological link between kidney disease and cardiovascular events.
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Affiliation(s)
- Santo Dellegrottaglie
- Zena and Michael A. Wiener Cardiovascular Institute and Marie-Josée and Henry R. Kravis Center for Cardiovascular Health, Mount Sinai Medical Center, New York, NY 10029-6574, USA
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27
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Jung HH, Kim SW, Han H. Inflammation, mineral metabolism and progressive coronary artery calcification in patients on haemodialysis. Nephrol Dial Transplant 2006; 21:1915-20. [PMID: 16554319 DOI: 10.1093/ndt/gfl118] [Citation(s) in RCA: 83] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Coronary artery calcification (CAC) is an extensive and common complication in patients with end-stage renal disease (ESRD). The aim of this study was to assess prospectively the change in CAC over a 2-year period and to identify the factors that may be associated with CAC progression in ESRD patients. METHODS The final analysis was performed on 40 of 43 stable haemodialysis patients who initially entered into the study. The study population underwent multirow spiral computed tomography to derive CAC scores at baseline and after a minimum of 12 months (24 months in 30 patients, 18 months in four, and 12 months in the remaining six patients). To provide a stable estimate that was unbiased with respect to the baseline CAC, square root-transformed CAC scores were used for the analyses of the changes in CAC. RESULTS The median CAC score was 191 (range, 0-2403) mm3 at baseline and increased to 253 (range, 0-2745) mm3 at follow-up (P < 0.001) and the median annualized change in square root-transformed CAC score was 1.48 (range, -0.95-8.64) mm3/year. The annualized change of the square root-transformed CAC score positively correlated with the time-integrated levels of C-reactive protein (R = 0.521, P = 0.001), phosphorus (R = 0.433, P = 0.005) and calcium x phosphorus product (R = 0.394, P = 0.012), but did not correlate with the levels of fetuin-A or lipid parameters. Even after adjusting for age, gender and baseline CAC score, C-reactive protein levels were independently associated with CAC progression. CONCLUSION These data suggest that chronic inflammation as well as altered mineral metabolism contributes to a rapid progression of CAC in ESRD patients. Additional, larger scale studies are required to confirm our findings.
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Affiliation(s)
- Hae Hyuk Jung
- Department of Internal Medicine, Kangwon National University Hospital, Hyoja-3-dong 17-1, Chunchon, Kangwon-do 200-947, Republic of Korea.
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Yuen D, Pierratos A, Richardson RMA, Chan CT. The natural history of coronary calcification progression in a cohort of nocturnal haemodialysis patients. Nephrol Dial Transplant 2006; 21:1407-12. [PMID: 16504981 DOI: 10.1093/ndt/gfl021] [Citation(s) in RCA: 52] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND End-stage renal disease (ESRD) is associated with a markedly increased cardiac calcification burden, as reflected by computed tomography scans of the heart. Nocturnal haemodialysis (NHD) is a novel form of renal replacement therapy which has multiple physiologic effects that may affect vascular calcification, including improvements in phosphate and uraemia control. The objective of the present study is the determination of the natural history of coronary calcification progression in patients converted to NHD, and the examination of the relationships between calcification risk factors and calcification progression in these patients. METHODS Thirty-eight ESRD patients were converted to NHD, and included in our observational cohort study. Coronary artery calcification scores (CACS) were documented at baseline and post-conversion (mean interscan duration 16+/-1 months). Other variables of interest included age, dialysis vintage, Framingham risk profile, phosphate binder and vitamin D usage, and plasma levels of calcium, phosphate and parathyroid hormone. RESULTS Our cohort was stratified according to baseline calcification burden (minimal calcification: CACS < or = 10 vs significant calcification: CACS > 10). Twenty-four patients had baseline CACS < or = 10. These patients demonstrated no change in coronary calcification after 1 year of NHD (from 0.7+/-0.5 to 6+/-3, P = 0.1). Fourteen patients had higher initial CACS at baseline (1874+/-696), and demonstrated a non-significant 9% increase over 1 year to 2038+/-740 (P = 0.1). Plasma phosphate and calcium x phosphate product were significantly reduced, as were calcium-based phosphate binder and antihypertensive usage. CONCLUSIONS Our study is the first to document CACS progression in a cohort of NHD patients. Further analysis of the effect of NHD on the physiology of cardiovascular calcification is required.
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Affiliation(s)
- Darren Yuen
- Department of Medicine, Division of Nephrology, Toronto General Hospital-University Health Network, University of Toronto, ON, Canada M5G 2C4
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Mehrotra R, Budoff M, Hokanson JE, Ipp E, Takasu J, Adler S. Progression of coronary artery calcification in diabetics with and without chronic kidney disease. Kidney Int 2006; 68:1258-66. [PMID: 16105059 DOI: 10.1111/j.1523-1755.2005.00522.x] [Citation(s) in RCA: 52] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Rapid progression of coronary artery calcification (CAC) has been reported among individuals with end-stage renal disease (ESRD). There is limited information on the progression of CAC during earlier stages of diabetic chronic kidney disease (CKD). METHODS In a prospective, cohort study of type 2 diabetic individuals (N = 90; normoalbuminuric diabetic controls, 30; diabetic nephropathy, DN, 60), electron-beam computed tomography (EBCT) was repeated at an average interval of 19 months. All scan images were acquired at end-systole to minimize interscan variability. In order to eliminate the dependence of the residual error from interscan variability on baseline CAC scores, square root transformed CAC scores were used for analyses of progression of coronary calcification. RESULTS Repeat EBCT scans were completed in 68 subjects (diabetic controls: 23; DN: 45). There was a highly significant relationship between the proportion of subjects with progressive CAC and renal disease-DN who progressed to ESRD, 80%; DN who did not progress to ESRD, 30%; and diabetic controls, 13% (P < 0.001). Similarly, the magnitude of change was significantly related to renal disease (DN who progressed to ESRD > DN who did not progress to ESRD > diabetic controls, P < 0.001). Using logistic regression and controlling for non-dialyzed DN, ESRD and inter-scan interval, advanced age was the only significant variable associated with progression of CAC. Finally, serum creatinine and baseline CAC score emerged as independent predictors for the magnitude of increase in CAC. CONCLUSION Progression of CAC is apparent among individuals with DN both before and after ESRD. However, the risk factors associated with progression of CAC may differ at different stages of CKD.
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Affiliation(s)
- Rajnish Mehrotra
- Division of Nephrology and Hypertension, Harbor-UCLA Medical Center, Torrance, California 90502, USA.
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Sigrist M, Bungay P, Taal MW, McIntyre CW. Vascular calcification and cardiovascular function in chronic kidney disease. Nephrol Dial Transplant 2005; 21:707-14. [PMID: 16263735 DOI: 10.1093/ndt/gfi236] [Citation(s) in RCA: 153] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Vascular calcification and arterial stiffening are independent predictors of all causes and cardiovascular mortality in chronic kidney disease (CKD). Few data are currently available comparing vascular calcification and its attendant functional cardiovascular consequences between CKD stage 4 patients and both peritoneal dialysis (PD) and haemodialysis (HD) (CKD stage 5) patients. METHOD We studied 134 subjects (60 HD, 28 PD and 46 CKD 4). Vascular calcification was quantified using multi-slice spiral CT scanning of a 5 cm standardized segment of superficial femoral artery. Pulse wave analysis and pulse wave velocity were assessed using applanation tonometry, to determine arterial compliance. Further digital arterial pulse wave analysis was used to measure systemic haemodynamic variables. All medications were recorded and biochemical variables were time averaged for the 6 months prior to entering the study. RESULTS Forty-seven percent of CKD 4 patients demonstrated vascular calcification as compared with CKD 5 (71% PD and 73% HD, P = 0.02). HD patients had higher calcification scores (median 121) than either PD (median 21) or CKD 4 (median 0) (P = 0.008). There were no significant differences in baseline characteristics between the groups. Comparing tertiles of patients (based on calcification score), increased calcification score was associated with a reduction in arterial compliance (mean PWV 8.9 +/- 1.1, 11 +/- 3.6, 11.3 +/- 3.7 m/s, P = 0.005). The degree of calcification did not influence systolic blood pressure (BP), diastolic BP or heart rate. However, more heavily calcified patients demonstrated significantly higher mean pulse pressures (58 +/- 19, 74 +/- 22 and 72 +/- 25 mmHg, P = 0.001), lower total peripheral resistance (1.5 +/- 1, 1.3 +/- 0.8, 0.9 +/- 0.4, P = 0.01) and higher stroke volume (84 +/- 25, 95 +/- 29, 106 +/- 39 ml, P = 0.01). More heavily calcified patients were significantly older and predominantly male. CONCLUSION This study has successfully utilized a novel technique for the quantification of calcification. We have demonstrated vascular calcification and associated cardiovascular dysfunction in CKD 4, PD and HD with significant differences between the groups. Thirty percent of individuals show no calcification, even those established on renal replacement therapy for a prolonged period of time. Further work is required to identify factors which promote progression of arterial calcification in those who are susceptible.
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Affiliation(s)
- Mhairi Sigrist
- Department of Renal Medicine, Derby City General Hospital, Derby, DE22 3NE, UK
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31
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Current World Literature. Curr Opin Nephrol Hypertens 2005. [DOI: 10.1097/01.mnh.0000172731.05865.69] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Malyszko J, Malyszko JS, Bachorzewska-Gajewska H. Cardiovascular risk in chronic renal disease and transplantation prevention and management. Expert Opin Pharmacother 2005; 6:929-43. [PMID: 15952921 DOI: 10.1517/14656566.6.6.929] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Cardiovascular disease (CVD) is the single best predictor of mortality in patients with chronic kidney disease and in kidney transplant recipients. These populations are considered to be at extraordinarily high risk for CVD and its complications. On the other hand, renal dysfunction should be considered as a CVD risk factor. The management of CVD in patients with chronic kidney disease is a special challenge for clinicians. In this article, major risk factors for CVD are presented, as well as diagnosis of coronary artery disease, acute coronary syndromes, its treatment modalities (pharmacological therapy and coronary revascularisation procedures), and outcomes in patients with chronic renal failure and kidney allograft recipients.
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Affiliation(s)
- Jolanta Malyszko
- Department of Nephrology and Transplantology, Medical University, 15-540 Bialystok, Zurawia 14, Poland.
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